To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.
Systematic review and network meta-analysis.
...Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.
Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.
36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.
Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.
PROSPERO CRD42017082553.
The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how ...to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 10
A/W and a specific detectivity of 2 × 10
Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm
.
Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low ...5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.
Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and ...regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.
Little is known about the epidemiologic features of syndactyly (SD) in Chinese newborns.
Using 2007-2019 data from the Chinese Birth Defects Monitoring Network, we conducted a prevalence analysis on ...overall, isolated and associated syndactyly according to birth year, maternal age, maternal residence, geographic region and infant sex, with special interests in time trends, perinatal outcomes and clinical phenotypes.
A total of 13,611 SD cases were identified among 24,157,719 births in the study period, yielding the prevalence of 5.63, 4.66 and 0.97 per 10,000 for overall, isolated, and associated SD, respectively. The prevalence of each type of SD exhibited an upward trend over the period. The prevalence of overall SD varied significantly by maternal residence (urban vs. rural, 6.69/10,000 vs. 4.35/10,000), maternal age (< 20 years, 5.43/10,000; 20-24 years, 5.03/10,000; 25-29 year, 5.65/10,000; 30-34 years, 6.07/10,000; ≥ 35 years, 5.76/10,000), geographic region (central, 5.07/10,000; east, 6.75/10,000; west, 5.12/10,000), and infant sex (male vs. female, 6.28/10,000 vs. 4.86/10,000). Newborns with associated SD were more likely to be born prematurely (29.2% vs. 10.6%) or with low birthweight (30.5% vs.9.8%) than those with isolated SD. The bilaterally, and unilaterally affected cases accounted for 18.4% and 76.7%, respectively. The feet were more frequently involved (64.3%) in those bilaterally affected cases, while right side preference (right vs left: 53.8% vs 46.2%) and upper limbs preference (hand vs foot: 50.8% vs 48.0%) were found in unilateral cases.
The prevalence of syndactyly in China is on the rise and notably higher than that in other Asian and European countries, highlighting the importance of investigating the etiology, epidemiology, and clinical implications of this condition in the Chinese population.
Freshwater fungi comprises a highly diverse group of organisms occurring in freshwater habitats throughout the world. During a survey of freshwater fungi on submerged wood in streams and lakes, a ...wide range of sexual and asexual species were collected mainly from karst regions in China and Thailand. Phylogenetic inferences using partial gene regions of LSU, ITS, SSU, TEF1α, and RPB2 sequences revealed that most of these fungi belonged to Dothideomycetes and Sordariomycetes and a few were related to Eurotiomycetes. Based on the morphology and multi-gene phylogeny, we introduce four new genera, viz.
Aquabispora
,
Neocirrenalia
,
Ocellisimilis
and
Uvarisporella
, and 47 new species, viz.
Acrodictys chishuiensis
,
A. effusa
,
A. pyriformis
,
Actinocladium aquaticum
,
Annulatascus tratensis
,
Aquabispora setosa
,
Aqualignicola setosa
,
Aquimassariosphaeria vermiformis
,
Ceratosphaeria flava
,
Chaetosphaeria polygonalis
,
Conlarium muriforme
,
Digitodesmium chishuiense
,
Ellisembia aquirostrata
,
Fuscosporella atrobrunnea
,
Halobyssothecium aquifusiforme
,
H. caohaiense
,
Hongkongmyces aquisetosus
,
Kirschsteiniothelia dushanensis
,
Monilochaetes alsophilae
,
Mycoenterolobium macrosporum
,
Myrmecridium splendidum
,
Neohelicascus griseoflavus
,
Neohelicomyces denticulatus
,
Neohelicosporium fluviatile
,
Neokalmusia aquibrunnea
,
Neomassariosphaeria aquimucosa
,
Neomyrmecridium naviculare
,
Neospadicoides biseptata
,
Ocellisimilis clavata
,
Ophioceras thailandense
,
Paragaeumannomyces aquaticus
,
Phialoturbella aquilunata
,
Pleurohelicosporium hyalinum
,
Pseudodactylaria denticulata
,
P. longidenticulata
,
P. uniseptata
,
Pseudohalonectria aurantiaca
,
Rhamphoriopsis aquimicrospora
,
Setoseptoria bambusae
,
Shrungabeeja fluviatilis
,
Sporidesmium tratense
,
S. versicolor
,
Sporoschisma atroviride
,
Stanjehughesia aquatica
,
Thysanorea amniculi
,
Uvarisporella aquatica
and
Xylolentia aseptata
, with an illustrated account, discussion of their taxonomic placement and comparison with morphological similar taxa. Seven new combinations are introduced, viz.
Aquabispora grandispora
(≡
Boerlagiomyces grandisporus
),
A. websteri
(≡
Boerlagiomyces websteri
),
Ceratosphaeria suthepensis
(≡
Pseudohalonectria suthepensis
),
Gamsomyces aquaticus
(≡
Pseudobactrodesmium aquaticum
),
G. malabaricus
(≡
Gangliostilbe malabarica
),
Neocirrenalia nigrospora
(≡
Cirrenalia nigrospora
), and
Rhamphoriopsis glauca
(≡
Chloridium glaucum
). Ten new geographical records are reported in China and Thailand and nine species are first reported from freshwater habitats. Reference specimens are provided for
Diplocladiella scalaroides
and
Neocirrenalia nigrospora
(≡
Cirrenalia nigrospora
). Systematic placement of the previously introduced genera
Actinocladium
,
Aqualignicola
, and
Diplocladiella
is first elucidated based on the reference specimens and new collections. Species recollected from China and Thailand are also described and illustrated. The overall trees of freshwater Dothideomycetes and Sordariomycetes collected in this study are provided respectively and genera or family/order trees are constructed for selected taxa.
Gastrointestinal microbiota may be involved in
associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential ...dysbiosis arising from
infection.
Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-
treatment, relative to 49
negative subjects.
In
positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in
positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between
and
,
,
,
,
were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased
after successful
eradication and more upregulated drug-resistant functional orthologs after failed treatment.
infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful
eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.
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Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence ...is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA) as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: −0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
Dual‐ion batteries (DIBs) are a viable option for large‐scale energy storage owing to their high energy density, low cost, and environmental friendliness. However, interfacial instability at both the ...cathode and anode in Li‐graphite DIBs (LG‐DIBs) contributes to poor cycling performance and failed energy storage, severely limiting their application potentials. Herein, a two‐pronged strategy is used to improve the interfacial stability, synergistically stabilizing the graphite cathode by applying a rigid/inert surface coating while building a 3D framework on the lithium anode. The resultant LG‐DIBs are ultrastable and achieve a long cycle life (capacity retention of 80% after 2700 cycles at 200 mA−1) in the all‐climate temperature range from −25 to 40 °C. Ex situ characterization reveals that the cathode–electrolyte interphase on graphite is stabilized by suppressing the electrolyte decomposition and reducing graphite exfoliation. Simultaneously, the framework constructed on the lithium anode induces uniform and dendrite‐free Li deposition owing to its 3D structure. This study not only contributes to the development of practical LG‐DIBs but also points out a promising research direction for other new types of batteries.
A two‐pronged approach is adopted to modify and strengthen the anode electrolyte interphase and cathode electrolyte interphase synergistically in Li‐graphite dual‐ion batteries. The battery life is significantly enhanced in all climates from −25 to 40 °C by inducing homogeneous Li deposition and suppressing successive decomposition of the electrolyte on the graphite cathode.
The emergence and spread of antibiotic resistance has posed a major threat to both human health and environmental ecosystem. Although the disinfection has been proved to be efficient to control the ...occurrence of pathogens, little effort is dedicated to revealing potential impacts of disinfection on transmission of antibiotic resistance genes (ARGs), particularly for free-living ARGs in final disinfected effluent of urban wastewater treatment plants (UWWTP). Here, we investigated the effects of chlorine disinfection on the occurrence and concentration of both extracellular ARGs (eARGs) and intracellular ARGs (iARGs) in a full-scale UWWTP over a year. We reported that the concentrations of both eARGs and iARGs would be increased by the disinfection with chlorine dioxide (ClO2). Specifically, chlorination preferentially increased the abundances of eARGs against macrolide (ermB), tetracycline (tetA, tetB and tetC), sulfonamide (sul1, sul2 and sul3), β-lactam (ampC), aminoglycosides (aph(2’)-Id), rifampicin (katG) and vancomycin (vanA) up to 3.8 folds. Similarly, the abundances of iARGs were also increased up to 7.8 folds after chlorination. In terms of correlation analyses, the abundance of Escherichia coli before chlorination showed a strong positive correlation with the total eARG concentration, while lower temperature and higher ammonium concentration were assumed to be associated with the concentration of iARGs. This study suggests the chlorine disinfection could increase the abundances of both iARGs and eARGs, thereby posing risk of the dissemination of antibiotic resistance in environments.
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•Impact of chlorination on eARGs pollution in UWWTPs were for the first time reported.•Chlorination disinfection enhanced both eARGs and iARGs pollution.•Extracellular tetM and sul1 were the most dominant eARGs in the final effluent.•E. coli showed a positive correlation with the total eARG concentration after chlorination.
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